Rational design of polysorbate 80 stabilized human serum albumin nanoparticles tailored for high drug loading and entrapment of irinotecan.

Human serum albumin (HSA) nanoparticles are considered to be versatile carrier of anticancer agents in efficiently delivering the drug to the tumor site without causing any toxicity. The aim of the study was to develop stable HSA nanoparticles (NPs) of drug irinotecan (Iro) having slightly water solubility and moderate HSA binding. A novel strategy of employing a hydrophilic non-ionic surfactant polysorbate 80 which forms protein-polysorbate 80 complex with increased affinity and improvement in Iro-HSA binding has been used to maximize the loading and entrapment efficiency of Iro in HSA-NPs. Bespoke nanoparticles with entrapment efficiency (79.09%) and drug loading of 9.62% could be achieved with spherical shape and particle size of 77.38 nm, 0.290 polydispersity index and -23.7 mv Zeta potential. The drug entrapment in nanoparticles was confirmed by Differential Scanning Calorimeter, Fourier Transformation Infrared Spectroscopy and Fluorescence Spectroscopy. In vitro release of Iro from NPs showed biphasic-release with initial burst followed by prolonged release upto 24 h. The short-term stability investigation of nanodispersion showed no significant changes in physicochemical properties of NPs. Long-term studies on freeze dried Iro-HSA-NPs indicated good stability of NPs up to 12 months. This is the first report for efficient fabrication of Iro delivery system based on HSA nanoparticles.

Betulinic acid, isolated from the leaves of Syzygium cumini (L.) Skeels, ameliorates the proteinuria in experimental membranous nephropathy through regulating Nrf2/NF-κB pathways.

Membranous nephropathy (MN) is associated with increased oxidative stress and inflammatory markers in the kidney. Betulinic acid (BA) is a potent antioxidant and anti-inflammatory compound isolated from the leaves of Syzygium cumini (L.) Skeels. In the present study, we investigated the effects of BA on experimental MN in rats and explored the mechanisms by which it enhances antioxidant activities and resolves inflammatory condition in experimental MN. Passive Heymann nephritis (PHN) was induced in Sprague-Dawley rats by a single tail vein injection of anti- Fx1A antiserum. The rats were orally administered BA (25 and 50 mg kg -1 d -1) or dexamethasone (DEX; 0.07 mg kg-1, reference compound) for 4 weeks after the induction of PHN. Blood, urine, and kidney tissue were collected for analysis at the end of the study. Treatment of PHN rats with BA or DEX significantly attenuated renal dysfunction, histopathological alterations and reduced immune complex deposition in the kidneys. Furthermore, BA ameliorated mRNA and protein expression of NF-κB, iNOS, TNF-α, Nrf2, HO-1 and NQO1 in the kidney. BA also restored malondialdehyde level and antioxidant enzyme activities in the kidney. In a nutshell, the protective effect of BA can be explained by its anti-inflammatory and anti-oxidant activities, which in turn is due to downregulation of NF-κB pathway and activation of Nrf2. The results indicated that BA can effectively suppress experimental PHN in rats by regulating Nrf2/NF-κB pathways.

Biophysical interactions of polyamidoamine dendrimer coordinated Fe3O4 nanoparticles with insulin.

Advanced delivery systems, such as nano/micro carriers have not been studied significantly for their molecular interactions with serum proteins and other biologically relevant macromolecules. Here, we investigated the effect of surface chemistry of iron oxide (Fe3O4) nanoparticles on molecular interactions with human insulin by fluorescence, XRD and FTIR spectroscopy. Nanoparticles of Fe3O4 were chemically modified as Fe3O4-glutathione (GSH) and Fe3O4-GSH-polyamidoamine generation 4 (PAMAM G4) dendrimer. Our results demonstrate that, Fe3O4 and its conjugates such as Fe3O4-GSH, Fe3O4-GSH-G4 quenched insulin fluorescence, indicating strong interactions between insulin protein molecule and Fe3O4. The fluorescence quenching constants Ksv were obtained as 0.0367 x 10(3), 0.0303 x 10(3) and 0.0131 x 10(3) M and the binding constant K were found to be 27.095, 8.404 and 6.026 mM for Fe3O4, Fe3O4-GSH and Fe3O4-GSH-PAMAM G4, respectively. Both the Ksv and K (binding constant) values revealed that the interaction of Fe3O4 with insulin to be stronger over to dendrimer conjugates. In addition, the FTIR spectra suggested that the presence of nanoparticles results in secondary structure alteration in the insulin conformation. The study implies the critical evaluation of new delivery systems in establishing the biocompatibility, especially when delivered by systemic route.